INVESTIGATING THE MIRROR NEURON SYSTEM IN AUTISM SPECTRUM DISORDER Project Summary One of the prominent clinical applications of the discovery of mirror neurons has been to explore how impairments in the mirror neuron system (MNS) might provide a mechanistic account for some of the core social communicative symptoms in autism spectrum disorder (ASD). The evidence for impairments in the MNS in ASD is conflicting, however there are significant gaps in the evidence and methodological limitations in the published studies. The proposed project addresses these limitations by building directly on the theoretical and methodological accomplishments of the other projects in this program project. We propose to investigate the MNS in 160 toddlers and preschoolers soon after they have been diagnosed with ASD (aged 24-42 months), and more specifically to explore the MNS in the context of a training study. This design will allow us to test the hypotheses that the onset of ASD is associated with an underlying systems-level impairment in the MNS and, furthermore, that targeted training leads to changes in MNS activity at the neural and behavioral levels. The project will address two specific aims. Aim #1: To explore the relations among behavioral and neuroimaging measures of the MNS in a large group of toddlers and preschoolers with ASD aged 24-42 months. The measures will include a battery of behavioral tasks tapping a range of behaviors associated with the MNS (from action prediction, to joint attention, instrumental helping and imitation). In addition we will collect EEG data on mu event-related desynchronization (mu ERD) and additional novel EEG measures in a variety of contexts. Analyses of these data will focus on identifying clusters of children with distinct profiles on these measures to be assessed with particular focus on links between behavioral and neural measures using latent class analytic approaches. Aim #2: To compare, in a randomized controlled design, the efficacy of two different targeted training paradigms on changes to behavioral and neural measures of the MNS. The children enrolled in the projectwill be randomized to one of two brief training protocols: (1) training to point; (2) training in object play. We predict that the pointing training, which is directly linked to joint attention and the MNS, will lead to more significant changes in mu ERD as well as on behavioral measures related to the MNS. We will also investigate whether there are reliable neural and behavioral predictors of response to both types of training that will help to develop a more personalized approach to planning early behavioral interventions for young children with ASD. The findings from these studies will address the controversial question of whether deficits in the MNS underlie the early manifestations of ASD, in at least in some children. If the intervention is successful, the findings will also provide the first evidence for the neural mechanisms that underlie one key component of early intervention that is known to be effective for many children with ASD.